T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways

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Abstract
Ligation of the T cell membrane antigen CD28 strongly enhances cytokine secretion in human T lymphocytes that are activated via T cell receptor (TcR)/CD3 or CD2 molecules. This study was undertaken to investigate whether, as has been indicated for activation via TcR/CD3, stimulation via CD28 is dependent on the activation of protein kinase C (PKC). Two inhibitors of PKC, 1‐alkyl 2‐methyl‐glycerol and staurosporine, caused a dose‐dependent inhibition of T cell proliferation induced by anti‐CD3 monoclonal antibodies (mAb). The induction of interleukin (IL)2 secretion was found to be more sensitive to the effects of the PKC inhibitors than the up‐regulation of IL2 receptor expression. In marked contrast, the anti‐CD28 mAb‐mediated enhancement of T cell proliferation and IL 2 secretion were insensitive to the action of either compound. We conclude that two independent signaling pathways may be operational in human T cells. The first used by TcR/CD3 depends on the activation of PKC, whereas the second is employed by CD28 and functions independently of PKC.